Born in Brooklyn to Jennie and Isaac Hook, who were Austrian - Jewish immigrants, Hook was a Socialist Party supporter during the Debs era when he was in high school. He earned his Bachelor's degree at the City College of New York in 1923, then his Ph.D. at Columbia University in 1927, where he was a student of the pragmatist philosopher John Dewey. Upon finishing his studies, Hook was hired by New York University, which employed him until his retirement in 1972. From 1948 to 1969 he was head of the department of philosophy.

At the beginning of his career, Hook achieved prominence as an expert on Karl Marx's philosophy and was himself a Marxist. He attended the lectures of Karl Korsch in Berlin in 1928 and did research at the Marx - Engels Institute in Moscow in the summer of 1929. At first, he wrote enthusiastically about the Soviet Union. In 1932 he supported the Communist Party's William Z. Foster when he ran for President of the United States. However, Hook broke completely with the Comintern in 1933, holding its policies responsible for the triumph of Nazism in Germany. He accused Stalin of putting "the needs of the Russian state" over the needs of the international revolution.

Hook remained, however, active on the far Left during the Great Depression. In 1933, along with James Burnham, Hook helped to organize the American Workers Party led by the Dutch born pacifist minister A.J. Muste. Hook also debated the meaning of Marxism with radical Max Eastman (who, like Hook, had studied under John Dewey at Columbia University) in a series of public exchanges. In the late 1930s, Hook assisted Leon Trotsky in his efforts to clear his name in a special Commission of Inquiry headed by Dewey, which investigated Stalinist charges made against Trotsky during the Moscow Trials.

The Great Purge prompted in Hook an increasing ambivalence toward Marxism. In 1939, Hook formed the Committee for Cultural Freedom, a short lived organization that set the stage for his postwar politics by opposing "totalitarianism" on the left and right. By the time of the Cold War Hook was a prominent anti-Communist, although he continued to consider himself a democratic socialist throughout his life.

In the late 1940s and early 1950s, Hook helped found Americans for Intellectual Freedom, the Congress for Cultural Freedom (CCF), and the American Committee for Cultural Freedom. These bodies — the CCF was most central — were, in part, funded by the Central Intelligence Agency through a variety of fronts, and sought to dissuade American liberals or Leftists from continuing to advocate cooperation with the Soviet Union as they had previously.

In the 1960s, Hook was a frequent critic of the New Left attaining notoriety for his outspoken support of the Vietnam War and for his defense of Governor Ronald Reagan's decision to remove Angela Davis from her position as a professor at UCLA because of her membership in the Communist Party (she was later rehired). He ended his career in the 1970s and 1980s as a fellow of the conservative Hoover Institution in Stanford, California.

The National Endowment for the Humanities selected Hook for the 1984 Jefferson Lecture, the U.S. federal government's highest honor for achievement in the humanities. Hook's lecture was entitled "Education in Defense of a Free Society."

Hook's memoirs, Out of Step, recount his life, his activism for a number of educational causes, as well as his recollections of Morris Cohen, John Dewey, Bertrand Russell, Mortimer J. Adler and Albert Einstein.

On May 23, 1985 Hook was awarded the Presidential Medal of Freedom by President Ronald Reagan.

In October of 2002, a conference marking the centennial of Hook's birth was organized by Matthew Cotter and Robert Talisse and held at the City University of New York Graduate Center in Manhattan.

Sydney Hook's book The Hero in History was a noticeable event in the studies devoted to the role of the Hero and Great Man in history and influence of the outstanding persons. Hook opposed all forms of determinism and argued (as William James did) that humans play a creative role in constructing social world and transforming the natural environment. Neither humanity nor its universe is determined, or finished. For Hook this conviction was crucial. He argues that when a society is at the crossroads choosing the direction of further development then an individual can turn to play a dramatic role and even become an independent power on whom depends the choice of the historical pathway. In his book Hook gives a great number of examples of the influence of great people and these examples are mostly associated with some crucial moments in history (revolutions, crises). This makes some scholars criticize him because

he does not take into account that an individual's greatest influence can be revealed not so much in the period of old regime's collapse, but in the formation period of a new one. Besides, he does not make clear the situation when alternatives appear either as the result of a crisis or as the result of Great Man's plan or intention without manifested crisis.

Hook introduced a division of historic personalities and especially leaders into eventful man and event making man depending on their influence on the historical process. For example, he considers Lenin as an event making man as in certain important respects he had changed the development direction not only of Russia but of the whole world in the 20th century.

Hook attaches great importance to accidents and contingencies in history thus opposing among others Herbert Fisher who made attempts to present history as ‘waves’ of emergencies following one after another.